Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Ferroptosis is a form of regulated cell death with an iron-dependent way that is involved in the development of various diseases. Whereas the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated.Methods: The FerrDb database and the previous studies were screened to explore the FRGs. The data of patients with IPF were obtained from the GSE70866 dataset. Wilcoxon's test and univariate Cox regression analysis were applied to identify the FRGs that are differentially expressed between normal and patients with IPF and associated with prognosis. Next, a multigene signature was constructed by the least absolute shrinkage and selection operator (LASSO)-penalized Cox model in the training cohort and evaluated by using calibration and receiver operating characteristic (ROC) curves. Then, 30% of the dataset samples were randomly selected for internal validation. Finally, the potential function and pathways that might be affected by the risk score-related differently expressed genes (DEGs) were further explored.Results: A total of 183 FRGs were identified by the FerrDb database and the previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (p < 0.05). There were five FRGs (aconitase 1 [ACO1], neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS], Ectonucleotide pyrophosphatase/phosphodiesterase 2 [ENPP2], Mucin 1 [MUC1], and ZFP36 ring finger protein [ZFP36]) identified as risk signatures and stratified patients with IPF into the two risk groups. The overall survival rate in patients with high risk was significantly lower than that in patients with low risk (p < 0.001). The calibration and ROC curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group. Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways.Conclusion: The five FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving the management strategies of IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, age-related interstitial pulmonary disease (ILD) with unknown etiology, significant morbidity, and unfavorable survival [1, 2]
A total of 183 ferroptosis-related genes (FRGs) were identified by the FerrDb database and the previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (p < 0.05)
The calibration and receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, age-related interstitial pulmonary disease (ILD) with unknown etiology, significant morbidity, and unfavorable survival [1, 2]. IPF was found at increased risk of severe coronavirus disease 2019 (COVID-19) due to sharing the same risk factors for severe COVID-19 [11], and as an independent risk for the development of lung cancer [12]. As a devastating disease with unknown etiology and difficult treatment, and the risk factor of other fatal diseases, there is an additional need to investigate the novel biomarkers for its diagnosis, treatment, and prognosis. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Whereas the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated
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